Superficially porous particles and methods of making and using same

ABSTRACT

Disclosed are porous-shell particles, methods of making the particles, and uses thereof. In one aspect, the porous-shell particles are superficially porous particles.

FIELD OF INVENTION

The present invention relates to porous-shell particles, methods ofmaking the particles, and uses thereof. In one aspect, the porous-shellparticles are superficially porous particles.

BACKGROUND

A porous-shell particle typically comprises a metal oxide core particlesurrounded by a porous shell around the core particle. Porous-shellparticles are typically either “totally porous,” having a porous coreand a porous shell, or “superficially porous,” having a substantiallysolid core and a porous shell. Porous-shell particles are used in avariety of applications, including for example, catalysis andchromatography. For most applications, micron scale porous particles areused, typically having diameters less than 500 μm.

A number of methods exist for making porous-shell particles. One methodinvolves a spray-drying technology, which is described in U.S. Pat. No.4,477,492 to Kirkland. In the spray-drying method, silica cores aremixed with colloidal silica sol, and the resultant mixture isspray-dried under high pressure at an elevated temperature (typicallyaround 200° C.). While this method has its advantages, particles made byspray-drying are often incompletely or inhomogeneously coated and areoften contaminated by undesired particles formed without the silicacore, which can be difficult to separate from the desired particles.

Another method for making porous-shell particles involves multilayertechnology, wherein metal oxide core particles are repeatedly coatedwith alternating layers of colloidal particles through electrostaticdeposition. Methods using this approach are described in U.S. Pat. No.3,505,785 and U.S. Patent Application No. 2007/0189944, both toKirkland. The multilayer layer method, however, can be time-consuming,often requiring multiple deposition steps. In addition, the multilayermethod is typically not optimal for particles having diameters less than5 μm.

Another approach is the coacervation method, wherein metal oxide coreparticles are coated with a coacervation layer comprised of an organicmaterial (typically a polymer) and colloidal metal oxide particles. Theorganic material is then removed, leaving behind metal oxide coreparticles having a porous shell comprising the colloidal particles. Thecoacervation method is more amenable to large-scale production relativeto other methods, but is still not optimal. Typically, difficultiesarise in forming the coacervation layer. In many instances, thecoacervation layer does not properly coat the metal oxide core, whichundesirably results in the formation of totally porous particlescomprising the colloidal metal oxide particles together with bare metaloxide core particles.

Accordingly, there is a need for improved methods for makingporous-shell particles, and in particular methods which can provideimproved particle and pore size distribution, as well as smallerporous-shell particles. These needs and other needs are satisfied by thepresent invention.

SUMMARY OF INVENTION

In accordance with the purpose(s) of the invention, as embodied andbroadly described herein, the invention, in one aspect, relates toimproved methods for making porous-shell particles, particles producedby the methods, and uses of the particles.

In one aspect of the present invention, superficially porous particlesare made by attaching an organic surface modifier to a solid metal oxidecore particle to provide a surface modified solid metal oxide coreparticle. A coating can then be formed on the surface modified solidmetal oxide core particle, wherein the coating comprises a continuouspolymeric phase bonded to the organic surface modifier and a particulatephase dispersed within the continuous polymeric phase. The continuouspolymeric phase can then be removed from the coating to provide asuperficially porous particle.

Also disclosed are a plurality of superficially porous particles,wherein at least one of the superficially porous particles is aggregatedwith a smaller totally porous particle.

Also disclosed are separation devices having a stationary phasecomprising a plurality of superficially porous particles, wherein atleast one of the superficially porous particles is aggregated with asmaller totally porous particle.

The advantages of the invention will be set forth in part in thedescription which follows, and in part will be obvious from thedescription, or may be learned by practice of the aspects describedbelow. The advantages described below will be realized and attained bymeans of the elements and combinations particularly pointed out in theappended claims. It is to be understood that both the foregoing generaldescription and the following detailed description are exemplary andexplanatory only and are not restrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagram of a disclosed superficially porous particle.

FIG. 2 is a micrograph of superficially porous particles prepared inExample 3.

FIG. 3 is a micrograph of superficially porous particles prepared by themultilayer method.

FIG. 4 is a graph of particle size distribution for the superficiallyporous particles prepared in Example 3.

FIG. 5 is a plot of pressure vs. velocity for the columns prepared inExample 7

FIG. 6 is a plot of pressure vs. flow-rate for the columns prepared inExample 7.

DETAILED DESCRIPTION OF THE INVENTION

Before the present compounds, compositions, particles, devices,articles, methods, or uses are disclosed and described, it is to beunderstood that the aspects described below are not limited to specificcompounds, compositions, particles, devices, articles, methods, or usesas such may, of course, vary. It is also to be understood that theterminology used herein is for the purpose of describing particularaspects only and is not intended to be limiting.

In this specification and in the claims that follow, reference will bemade to a number of terms that shall be defined to have the followingmeanings:

Throughout this specification, unless the context requires otherwise,the word “comprise,” or variations such as “comprises” or “comprising,”will be understood to imply the inclusion of a stated component or stepor group of components or steps but not the exclusion of any othercomponent or step or group of components or steps.

It must be noted that, as used in the specification and the appendedclaims, the singular forms “a,” “an” and “the” include plural referentsunless the context clearly dictates otherwise. Thus, for example,reference to “a particle” includes mixtures of two or more suchparticles.

“Optional” or “optionally” means that the subsequently described eventor circumstance can or cannot occur, and that the description includesinstances where the event or circumstance occurs and instances where itdoes not.

Ranges may be expressed herein as from “about” one particular value,and/or to “about” another particular value. When such a range isexpressed, another aspect includes from the one particular value and/orto the other particular value. Similarly, when values are expressed asapproximations, by use of the antecedent “about,” it will be understoodthat the particular value forms another aspect. It will be furtherunderstood that the endpoints of each of the ranges are significant bothin relation to the other endpoint, and independently of the otherendpoint.

As used herein, a “wt. %” or “weight percent” or “percent by weight” ofa component in a composition or mixture, unless specifically stated tothe contrary, is based on the total weight of the composition of mixturein which the component is included.

As used herein, “median particle size” refers to the median or the 50%quantile of total particle size distribution.

As used herein, “coacervation” refers to a process by which a porousshell comprising a particulate phase is formed around a core particle.The coacervation process comprises forming a coating also referred to asa “coacervation layer” around the core particle. The “coacervationlayer” comprises a continuous polymeric phase and a dispersedparticulate phase. The “coacervate,” in one aspect, is the polymer ofthe continuous polymer phase. The particulate phase typically comprisesparticles that are smaller than the core particle. After formation ofthe coacervation layer, the continuous polymeric phase can be removed toprovide a porous shell comprising the remaining particulate phase formedaround a core particle. The term “coacervation” refers to a processdefined herein, and is not restricted to any particular composition orchemical reaction. Likewise, the terms “coacervation layer,” and“coacervate” refer to compositions that are not restrictive to anyparticular method for making the coacervation layer or coacervate.

Disclosed are compounds, compositions, and particles that can be usedfor, can be used in conjunction with, can be used in preparation for, orare products of the disclosed methods and compositions. These and othermaterials are disclosed herein, and it is understood that whencombinations, subsets, interactions, groups, etc. of these materials aredisclosed that while specific reference of each various individual andcollective combinations and permutation of these compounds may not beexplicitly disclosed, each is specifically contemplated and describedherein. For example, if a number of different polymers and coreparticles are disclosed and discussed, each and every combination andpermutation of the polymer and core particles are specificallycontemplated unless specifically indicated to the contrary. Thus, if aclass of polymers A, B, and C are disclosed as well as a class of coreparticles D, E, and F and an example of a combination particle coatedwith the polymer, A-D is disclosed, then even if each is notindividually recited, each is individually and collectivelycontemplated. Thus, in this example, each of the combinations A-E, A-F,B-D, B-E, B-F, C-D, C-E, and C-F are specifically contemplated andshould be considered disclosed from disclosure of A, B; and C, D, E, andF; and the example combination A-D. Likewise, any subset or combinationof these is also specifically contemplated and disclosed. Thus, forexample, the sub-group of A-E, B-F, and C-E are specificallycontemplated and should be considered disclosed from disclosure of A, B,and C; D, E, and F; and the example combination A-D. This conceptapplies to all aspects of this disclosure including, but not limited to,steps in methods of making and using the disclosed particles. Thus, ifthere are a variety of additional steps that can be performed it isunderstood that each of these additional steps can be performed with anyspecific embodiment or combination of embodiments of the disclosedmethods, and that each combination is specifically contemplated andshould be considered disclosed.

In one aspect, the present invention relates to an improved coacervationmethod for making porous-shell particles, including superficially porousparticles. It was discovered that, prior to forming a coacervate layeron the surface of a core particle, the core particle can beadvantageously modified with a material that enhances the formation ofthe coacervate coating. The disclosed methods offer a number ofadvantages, including providing for superficially porous particleshaving smaller particle sizes (e.g., from about 0.5 to about 10 μm) andsmaller size distributions than conventional methods known in the art.The methods also provide for particles exhibiting improved performancein separation devices.

Generally, the core particle can be a porous or non-porous particle. Inone aspect, the core particle is a non-porous, solid particle. As usedherein, a “solid particle” is one that is not a liquid or a gas. Solidparticles can be pervious or impervious. For certain chromatographicapplications, it can be preferable to use impervious solid particles(i.e., particles having a low pore volume), such that materials passingthrough a zone of such particles do not enter the interior of the core.Typically, pore volumes for impervious cores are less than about 0.005cm³/gm.

The core particle can have any desired shape, which will generallydepend on the targeted application. For chromatographic applications,suitable shapes include without limitation spheres, rings, polyhedra,saddles, platelets, fibers, hollow tubes, rods and cylinders, andmixtures of any two or more such shapes. In one aspect, the core issubstantially spherical. Spherical cores can be easily packed and arethus desirable for certain applications, such as chromatography.

The composition of the core particle is not critical, provided that thecore be capable of reacting or bonding to an affinity material whichaids in the formation of the coacervate coating around the coreparticle. Suitable core materials include without limitation glasses,sands, metals, metalloids, ceramics, and combinations thereof.

It should be understood that the shape, composition, and size of thecore particles can be distributional properties that vary. To that end,it is not required that all the core particles in a given populationcomprise a uniform size, composition, or shape. It is thereforecontemplated that according to aspects of the invention, all orsubstantially all core particles have the same or similar size, shape,and composition. Alternatively, it is also contemplated that accordingto other aspects of the invention, the shape, composition, and size ofcore particles in a given population can vary.

In one aspect, the core particle comprises a metal oxide, such as arefractory metal oxide. In a further aspect, the core particle is asolid metal oxide particle. Exemplary metal oxides include withoutlimitation silica, alumina, titania, zirconia, ferric oxide, antimonyoxide, zinc oxide, and tin oxide. In another aspect, the core particlecan comprise silica, alumina, titania, zirconia, or a combinationthereof. In a further aspect, the core particle comprises silica. In oneaspect, the metal oxide particle with surface hydroxyl groups can bemodified with a disclosed surface modifier.

The core particles can have any desired size, depending on the desiredsize of the porous-shell particle. Generally, the core particle islarger than the colloidal particles used to form the porous shell. Inone aspect, the core particle has a size ranging from about 20% to about99% of the total particle size.

In one aspect, the core particles have a median particle size from about0.1 μm to about 100 μm, including without limitation core particleshaving a median particle size from about 0.5, 2, 4, 6, 8, 10, 12, 14,16, 18, 20, 30, 40, 50, 60, 70, 80, and 90 μm. It will be apparent thedisclosed methods are useful for smaller particles, e.g. porous-shellparticles having median particle sizes less than about 10 μm, or lessthan about 5 μm. Such particles can be prepared from corresponding coreparticles having median particle sizes of from about 0.1 to about 10 μm,or from about 0.1 to about 5 μm, or from about 0.1 to about 3 μm. Inspecific aspects, a core particles (e.g. silica) have a median particlesize of from about 1 to about 3 μm, including without limitation 1, 1.2,1.5, 1.8, 1.9, 2, 2.2, 2.5, 2.7, and 3 μm.

Depending on the conditions used during coacervation, the median size ofthe core particle can change throughout the process. For example, aftersintering, the core of the porous-shell particle can be smaller than thecore used as the starting material. To that end, in one aspect, thosemedian sizes disclosed above refer to core sizes prior to processing. Inanother aspect, the size of the core remains substantially similar afterprocessing, and those sizes disclosed above also refer to the size ofthe core in the final porous-shell particle. In a further aspect, thosesizes disclosed above refer to the size of the core in the finalporous-shell product, regardless of the size of the starting materialcore. Particle size can be determined using methods known in the art,for example through the use of a Coulter Counter, which can also countparticles and thus provide particle size distributions.

The particle size distribution of the core particles can vary dependingon the composition of the core particle and the method in which the coreparticle was made and/or processed. In one aspect, the core particleshave a particle size distribution of less than about 20% of the medianparticle size, including for example, less than about 15%, less thanabout 10%, or less than about 5% of the median particle size. In afurther aspect, the core particles have a particle size distribution offrom about 0.5% to about 10% of the median particle size, includingwithout limitation particle size distributions of from about 0.5% toabout 8%, 0.5% to about 6%, and from about 0.5% to about 5% of themedian particle size.

Solid metal oxide core particles can be made by various known processes,including processes disclosed in U.S. Pat. No. 3,634,588 to Steitz etal., U.S. Pat. No. 4,775,520 to Unger et al., and U.S. Pat. No.4,983,369 to Barder et al., each of which is incorporated herein by thisreference for its teaching of methods for making metal oxide particles.Metal oxide core particles can also be provided by sintering porousparticles (e.g., commercially available porous particles) to form solidparticles. When certain metal oxide particles are used, such as silica,commercially available glass beads (Potters Industries, Inc., ValleyForge, Pa., U.S.A.), can be elutriated and fractionated into desiredsize distributions. Such commercial products are not typically purified,but can be surface-purified by treatment with acid, such as hydrochloricacid or nitric acid, to remove contaminating materials, if present.

In a specific aspect, when silica particles are used, the processdisclosed in U.S. Pat. No. 4,775,520 to Unger et al., referenced above,is used to provide the core silica particles. In accordance with thismethod, small silica “seed” nanoparticles obtained from high puritysilica sol are prepared by a method such as described by Stober et al.,J. Colloid Interface Sci. 26 (1968) 62-69, which is incorporated hereinby this reference for its teaching of the preparation of silica seedparticles. The silica seed particles are then grown into cores of adesired size by depositing silica produced by the slow hydrolysis oftetraethyl-o-silicate by dilute ammonia while the seed particles aresuspended in solution. The core particles produced by this method cancontain micropores, and thus can be solidified by a method such asautoclaving or sintering, discussed above.

Depending on the processing method, it can be useful to further modify acore particle produced by one of the methods disclosed above prior tocoating or reacting the core particle with another material, or prior toadding the organic surface modifier used as an aid during thecoacervation step, discussed below. For example, if sintering is used inthe making or processing of the particle, it can be desirable torehydroxylate the surface of the core particle prior to reacting theparticle further. Rehydroxylation can be carried out by a number ofmethods, including by placing the core particles in boiling and/orstrong hydrochloric or nitric acid, or by the procedures described in J.Kohler and J. J. Kirkland, J. Chromatogr. 385 (1987) 125, which isincorporated herein by this reference for its teaching of surfacerehydroxylation.

Prior to forming the coacervate layer around the core particle, it canbe useful to first attach an organic surface modifier to the coreparticle, as briefly discussed above. When the coacervation layercomprises a continuous polymer phase having a dispersed particulatephase therein, the organic surface modifier can, in various aspects,enhance the binding of the continuous polymer phase to the coreparticle. In certain aspects, the organic surface modifier can bond tothe coacervate layer and/or the continuous polymer phase. In furtheraspects, the organic surface modifier can covalently bond to thecontinuous polymer phase. For example, the organic surface modifier canbe a residue from which a polymerization can begin and/or a residue towhich an oligomer or polymer can covalently bond. Thus, in variousaspects, the organic surface modifier functions to aid in the formationof the coacervation layer around the core particle by attracting thecontinuous polymer phase or precursor(s) thereof to the surface of thecore particle. By doing so, the particulate phase of the coacervationlayer, which is or becomes dispersed in the continuous polymer phase, isalso thereby attracted to the surface, allowing a well-defined porousshell to from around the core, once the continuous polymer phase isremoved.

The composition of the organic surface modifier is not critical,provided that it provides the desired result. Generally, however, theorganic surface modifier is chemically similar (or can bond or react) tothe polymer or precursor(s) thereof used to form the coacervation layer.In one aspect, the organic surface modifier has the same or a similarfunctional group as the polymer in the coacervation layer.

In certain aspects, when the continuous polymer phase comprisespoly(urea-formaldehyde) and/or poly(melamine), the organic surfacemodifier comprises a functional group that can react with a precursorurea, formaldehyde, or melamine monomer; or oligomer or polymer thereof.In the specific case of poly(urea-formaldehyde) or poly(melamine),suitable functional groups include electrophilic or nucleophilic groupsthat can react with urea, formaldehyde, melamine, or an oligomer orpolymer thereof. Exemplary functional groups that can react withformaldehyde include without limitation alcohols, thiols, amines,amides, among others. A specific example is a ureido residue. Suitablefunctional groups that can react with urea and/or melamine includeketones, aldehydes, isocyanates, acryl groups, epoxy groups, glycidoxygroups, among others.

In one aspect, the organic surface modifier is covalently bonded to thesurface of the core particle. In a further aspect, the organic surfacemodifier is covalently bonded to one or more surface oxygen atoms (i.e.,formerly hydroxyl groups, prior to attaching the organic surfacemodifier) of the core metal oxide particle. In a still further aspect,the organic surface modifier is covalently bonded to the surface of thecore particle through one or more M—O— bonds, wherein M is Si, Al, Ti,Zr, Fe, Sb, Zn, or Sn.

In specific aspects, the organic surface modifier can comprise anorganosilane residue that is bonded to the surface of a metal oxideparticle (e.g. a silica particle). A variety of organosilane residuescan be used, provided they are capable of bonding to the continuouspolymer phase of the coacervation layer. In one aspect, the organosilanecomprises one or more of those functional groups discussed above. In afurther aspect, the organosilane is (aminopropyl)triethoxysilane,(3-trimethoxysilylpropyl)diethylenetriamine,(3-glycidoxypropyl)trimethoxysilane, (isocyanatopropyl)triethoxysilane,(isocyanatopropyl)triethoxysilane, (isocyanatopropyl)triethoxysilane, or(isocyanatopropyl)triethoxysilane. In a further aspect, the organosilaneis not (aminopropyl)triethoxysilane,(3-trimethoxysilylpropyl)diethylenetriamine,(3-glycidoxypropyl)trimethoxysilane, (isocyanatopropyl)triethoxysilane,(isocyanatopropyl)triethoxysilane, (isocyanatopropyl)triethoxysilane, or(isocyanatopropyl)triethoxysilane.

In further aspects, when the continuous polymer phase comprisespoly(urea-formaldehyde), the organosilane used to form the organicsurface modifier can comprise one or more of(aminopropyl)triethoxysilane,(3-trimethoxysilylpropyl)diethylenetriamine,(3-glycidoxypropyl)trimethoxysilane, or ureidopropyltrimethoxysilane.

In a further aspect, the organic surface modifier is itself an oligomeror polymer, which can be the same or different than the polymer used inthe coacervation layer. The oligomer or polymer can be physisorbedand/or bonded to the surface of the core particle. Thus, the oligomer orpolymer can be covalently or non-covalently (e.g., electrostatically,hydrophilically/hydrophobically, hydrogen bonded, coordinated, etc.)bonded to the surface of the core particle, or can be merely physisorbedwhere no chemical bond exists. An example of a polymer that can becovalently bonded to a surface of a core particle ispoly(1-vinylpyrrolidone-co-2-dimethylaminoethyl methacrylate).

In one aspect, the organic surface modifier is noncovalently bonded(e.g., hydrogen bonded, coordinated, etc.) and/or physisorbed to thesurface of the core particle. For example, if the continuous polymerphase of the coacervation layer comprises poly(urea-formaldehyde), theorganic surface modifier can be poly(urea-formaldehyde). In this aspect,it can be preferable that the poly(urea-formaldehyde) used as theorganic surface modifier is oligomeric, or at least smaller than thepolymer used in the coacervation layer. In this exemplary aspect, theorganic surface modifier becomes a part of the continuous polymer phase.In other aspects, polymers such as polyethylenimine, polyacrylamide, orpoly(melamine) can be noncovalently bonded or physisorbed to the surfaceof the core particle.

In one aspect, the method for making the superficially porous particlesfirst comprises providing a solid metal oxide core particle having anorganic surface modifier attached to a surface thereof. This step can beaccomplished, in various aspects, by attaching an organic surfacemodifier to the solid metal oxide core particle to provide a surfacemodified solid metal oxide core particle, as discussed above. Thesurface modifier can be attached to the core particle through variousmeans. When the modifier is covalently bonded to the surface of the coreparticle, a reactive residue, polymer, oligomer, or polymer can bereacted with one or more surface hydroxyl groups, or another functionalgroup on the surface, under conditions effective to form a covalentbond. Various methods for modifying the surface of metal oxide particlesare known in the art.

When the modifier is a polymer, for example, the core particle can beplaced in a solution of one or more monomers, and the one or moremonomers can be polymerized, thereby adhering the polymer or oligomer tothe surface of the core, through a chemical bond, physisorption, orboth. In a specific aspect, a core particle can be placed in a solutionof urea and formaldehyde, and the pH of the solution can be adjusted tofrom about 3.5 to about 5.5, to thereby produce a desired oligomer orpolymer of urea and formaldehyde, which can chemically react with afunctional group attached to the surface and/or physisorb to the surfaceof the core particle during or after polymerization. Prior to droppingthe pH to from about 3.5 to about 5.5, the pH of the solution shouldtypically be basic, e.g. from about pH 10-11, to prevent undesiredpolymerization. Following the formation of the oligo- orpoly(urea-formaldehyde), the pH of the solution can be raised, forexample to about pH 9, to aid in breaking up excesspoly(urea-formaldehyde) that is formed. In this aspect, if the pH is toolow (e.g., less than 3) during the formation of the oligo- orpoly(urea-formaldehyde) surface modifier, cross-linking of the oligo- orpoly(urea-formaldehyde) can be too extensive, resulting in the formationof undesired aggregates. Likewise, if the pH is too high (e.g., greaterthan 6), cross-linking can be too minimal, and a coating may not form onthe core particle. It is understood that the above disclosed process forpreparing a core particle modified with an oligo- orpoly(urea-formaldehyde) is suitable for instances wherein the oligo- orpoly(urea-formaldehyde) is chemically bonded and/or physisorbed to thecore particle.

Once the surface modified core particle is provided, the coacervationcoating can be formed or applied to the particle. Generally, thecoacervation coating comprises a continuous polymeric phase bonded tothe organic surface modifier and a particulate phase dispersed withinthe continuous polymeric phase. As discussed above, the coacervationcoating or a portion thereof adheres or bonds to the organic surfacemodifier to enhance the formation of the porous shell around the coreparticle.

The polymeric phase can comprise any suitable polymer which can comprisea dispersed particulate phase and which can covalently, noncovalently,or physically bond to the organic surface modifier. In one aspect, asuitable polymer is cross-linkable polymer. It will be apparent that thecross-linking ability of the polymer can aid in the dispersion of theparticulate phase within the polymer. In one aspect, the continuouspolymer phase comprises a poly(urea-formaldehyde), poly(melamine), or acombination, or copolymer thereof.

The particulate phase generally comprises metal oxide particles, whichare typically smaller in size than the core particle. The composition ofthe particulate phase can comprise any of those metal oxides describedabove. In one aspect, the particulate phase comprises a refractory metaloxide particle. Exemplary metal oxides include without limitationsilica, alumina, titania, zirconia, ferric oxide, antimony oxide, zincoxide, and tin oxide. In another aspect, the particulate phase cancomprise silica, alumina, titania, zirconia, or a combination thereof.In a further aspect, the particulate phase comprises silica.

The particles of the particulate phase can have any desired size.Preferably, the particulate phase particles are smaller in size than thecore particle, such as, for example, about 10%, 25%, 50%, or 75% smallerthan the core particle, or smaller. In one aspect, the particles of theparticulate phase are nano-scale sized particles. For example, theparticles can have a size or average diameter from about 1 nm to about1000 nm, including without limitation particles having an averagediameter from about 1 nm to about 100 nm, from about 1 nm to about 50nm, from about 1 nm to about 30 nm, from about 1 nm to about 15 nm, orfrom about 1 nm to about 10 nm. The particles of the particulate phasecan have any suitable particle size distribution, including for example50%, 30%, 20%, 10%, 5%, or less of the median particle size. In oneaspect, the particulate phase comprises silica, and is formed fromsilica sol, or colloidal silica.

The coacervate composition can be provided using various methods. In oneaspect, the coacervate composition is formed and coated onto themodified core particle in one pot. In a further aspect, the coacervatelayer can be formed by placing the core particles in a solution ordispersion of one or more monomers used to form the continuous polymerphase and particles used to form the particulate phase. The monomers canbe polymerized into oligomers or polymers, which will comprise dispersedtherein the particulate phase, and which can bind to the modified core.In a specific aspect, the core particle can be placed into a solution ordispersion of particles, such as silica sol. The solution or dispersioncan then be agitated, to thereby reduce agglomeration of the particles.Then, the monomer(s) can be added into the solution or dispersion,followed by the polymerization of the monomers.

In a further specific aspect, when the continuous polymer phasecomprises poly(urea-formaldehyde), the modified core particle can beadded to a solution or dispersion of silica sol, followed by optionalagitation, and then urea and formaldehyde can be added to the solution,followed by the polymerization of the urea and formaldehyde under a pHeffective to form the desired continuous polymer phase (e.g., lower than2, and preferably 1.5).

Once the coacervate coating is formed, the continuous polymeric phaseand/or the organic surface modifier can be removed from the coating toprovide a porous-shell particle. Generally, the polymeric phase isremoved by heating the particles at a temperature sufficient to burn offthe polymeric phase, for example from about 500° C. to about 800° C. fora sufficient time (e.g., about 2 to 3 hours). If desired, the formedporous-shell particles can be sintered to solidify and strengthen theparticles and/or reduce undesired micropores in the porous shell (i.e.the particulate phase). Sintering can be accomplished, for example, at atemperature of from about 900° C. to about 1500° C., including forexample, 1000° C. If desired, the surface of the particles can berehydroxylated, using methods discussed above. Additionally, theparticles can be size-classified by liquid elutriation.

The disclosed porous-shell particles can be made by the disclosedmethods, or other methods. The porous-shell particles can have any shapeor composition discussed above. For example, with reference to FIG. 1, aspherical porous-shell particle 100 generally comprises a particlediameter 105, a solid core 110 having a solid core diameter 115, whichis surrounded by a porous shell 120 having a corresponding shellthickness 125.

In one aspect, the solid core has a size ranging from about 20% to about99% of the total particle size, including without limitation 30%, 40%,50%, 60%, 70%, 80%, or 90% of the total particle size. The porous outershell typically comprises particles from the particulate phase,discussed above. The shell can have any desired porosity. In one aspect,the particles have shells having substantially ordered pores with medianpore sizes from about 15 to about 1000 Å, including for example about20, 50, 100, 200, 500, 700, 800, or 900 Å median pore sizes. In aspecific aspect, the core particles comprise shells having substantiallyordered pores with a median pore size from about 100 to about 200 Å,including for example, about 120 Å median pore size. Likewise, the porescan have any corresponding pore volume, including pore volumes of fromabout 0.1 to about 10 cm³/g, such as from about 0.1 to about 0.5 cm³/g.

The porous-shell particles generally have a surface area of from about 5to about 1000 m²/g. For example, the porous-shell particles can have asurface area of from about 5 to about 200 m²/g, including withoutlimitation about 120 m²/g.

The porous-shell particles can have any desired size, depending on thesize of the core particle and the shell thickness. In one aspect, theparticles have a median particle diameter from about 0.1 to about 100μm, including for example, particles having a median diameter from about0.1 to about 50 μm, 0.1 to about 30 μm, 0.1 to about 20 μm, 0.1 to about10 μm, or 0.5 to 10 μm. In one aspect, the disclosed methods are usefulfor small particles, e.g. those having a median particle diameter offrom about 0.1 to about 5 μm, including for example, particles having amedian particle diameter of about 3 μm.

In one aspect, superficially porous particles are present as a pluralityof particles, wherein at least one of the superficially porous particlesis aggregated with smaller totally porous particle. With reference tothe micrograph of FIG. 2, for example, it can be seen that at least oneof the superficially porous particles 210 comprising a solid silica coreand a porous silica shell is aggregated with a smaller totally porousparticle 215. In one aspect, the plurality of particles is made by thedisclosed methods.

It will be apparent that when using the disclosed coacervation methods,a small amount of dimers, trimers and aggregates of the particles canform. At least two types of dimers/trimers/aggregates can form duringthe disclosed coacervation methods. First, dimers/trimers/aggregatescomprising two or more superficially porous particles can form.Typically, each particle in such dimers/trimers/aggregates are similarin size, thus allowing these dimers/trimers/aggregates to be removed byprocesses such as elutriation from the desired particles. Second, theinventive coacervation methods also produce another type ofdimer/trimer/aggregate that comprises one or more superficially porousparticles aggregated with one or more smaller totally porous particles.This type of dimer/trimer/aggregate can often not be removed from thedesired particles, due to their size similarities. Generally, thetotally porous particle of such a dimer/trimer/aggregate comprises aparticle used in the particulate phase, without the solid core, whichtends to form at about the same rate as the porous shell. It should beappreciated, however, this type of dimer/trimer/aggregate does nottypically produce any substantial deleterious effects when using theparticles in applications, for example chromatography.

By contrast, the multilayer method for producing superficially porousparticle does not result in dimers/trimers/aggregates comprised of oneor more superficially porous particles and one or more smaller totallyporous particles. This can be seen, for example, in FIG. 3, which showssuperficially porous silica particles made by the multilayer method. Themultilayer method, however, can result in the first type ofdimer/trimers/aggregates discussed above, which comprise two or moresuperficially porous particles aggregated together. As discussed above,such dimers/trimers/aggregates are typically easily removed from thedesired particles by a process such as elutriation.

The porous-shell particles can be used in any desired application. Inone aspect, the porous shell particles are used in a separation device.The separation device can, for example, comprise the plurality ofparticles discussed above. The separation device can also comprise aproduct of the disclosed methods. Examples of suitable separationdevices include chromatographic columns, chips, solid phase extractionmedia, pipette tips and disks.

EXAMPLES

The following examples are put forth so as to provide those of ordinaryskill in the art with a complete disclosure and description of how thecompounds, compositions, and methods described and claimed herein aremade and evaluated, and are intended to be purely exemplary and are notintended to limit the scope of what the inventors regard as theirinvention. Efforts have been made to ensure accuracy with respect tonumbers (e.g., amounts, temperature, etc.) but some errors anddeviations should be accounted for. Unless indicated otherwise, partsare parts by weight, temperature is in degrees Centigrade (° C.) or isat ambient temperature, and pressure is at or near atmospheric. Thereare numerous variations and combinations of reaction conditions, e.g.,component concentrations, component mixtures, desired solvents, solventmixtures, temperatures, pressures and other reaction ranges andconditions that can be used to optimize the product purity and yieldobtained from the described process. Only reasonable and routineexperimentation will be required to optimize such process conditions. Inthe following examples, particle size was measured using Beckman CoulterCounter instruments.

Example 1 Preparation of Surface Modified Core Particles (I)

In a first example, core particles of 1.90-μm diameter were prepared bygrowing 600 nm silica sol “seed” particles. Specifically, 600 nm silicasol “seed” particles were prepared by 40 mL of EtOH, 50 mL of ammoniumhydroxide, and 10 mL tetraethoxysilane (TEOS) at 40° C. according toStober et al., J. Colloid and Interface Sci. 26, 62-69 (1968). Asolution “A” containing 400 ml of TEOS and 1600 ml of ethanol, and asolution “B” containing 480 ml of NH₄OH, 720 ml of H₂O and 800 ml ofethanol were added separately and continuously at a flow rate of 5ml/min into the 600 nm silica sol “seed” particles in a flask maintainedat 40° C. until the median particle size reached about 1.90 μm. Then, asolution of 25 ml of ureidopropyltrimethoxysilane (Gelest, catalog #SIU9058.0) in 25 ml of ethanol was added into the above solution at aflow rate of 5 ml/min. The mixture was stirred overnight at 40° C. Thesilica cores were centrifuged at 1300 rpm for 10 minutes, and reslurriedin one liter of H₂O and centrifuged at 1300 rpm for 10 minutes. Thecores were washed several times by reslurrying in water followed bycentrifugation. Finally the silica cores were in one liter water. Asmall sample was taken out, dried, and sent out for carbon analysis(Microanalysis, Wilmington, Del.). The cores exhibited 0.50% to 1.0%carbon. Another small sample was sintered at 1000° C. for 2 hours. Thesize after sintering was measured as 1.67 μm diameter by the CoulterCounter, and the surface area was measured as <1 m²/g by the Tristarinstrument (Micromeritics, Norcross, Ga.).

To the above silica cores, were added 32 g of urea (Aldrich, catalog#U5128) and 54.8 g of formaldehyde (Aldrich, catalog# 252549). The pHwas adjusted to 4.0 by nitric acid. After 4 hours, the pH was adjustedagain to 4.0. The solution was stirred at room temperature overnight.The silica solution or dispersion was centrifuged at 1300 rpm for 10minutes, and was reslurried in one liter of 2 nm sol solution andsonicated for 30 minutes. The cores were centrifuged at 1300 rpm for 10minutes, reslurried in one liter of water, and centrifuged at 1300 rpmfor 10 minutes. The above centrifugation and reslurry step was repeated4 times until there was no polymer floating in the upper layer undermicroscope. Finally the silica cores were reslurried in one liter ofacetone, filtered, allowed to dry in the air for several hours. Thesilica was then dried at 100° C. overnight. The final weight was ˜100 g.A small sample was taken out, dried, and sent out for carbon analysis(Microanalysis, Wilmington, Del.). The cores exhibited 2.0% to 4.0%carbon.

Example 2 Preparation of Surface Modified Core Particles (II)

The 1.2 μm silica cores were prepared by the procedure in example 1except the size was allowed to grow to 1.2 μm, and the core surface wasalso modified according to the procedure in example 1 withureidopropyltrimethoxysilane and urea/formaldehyde. A small sample wassintered at 1000° C. for 2 hours. The size after sintering was measuredas 1.05 μm diameter by the Coulter Counter, and surface area wasmeasured as <1 m2/g by the Tristar instrument (Micromeritics, Norcross,Ga.).

Example 3 Preparation of Superficially Porous Particles (I)

Superficially porous particles were made by the coacervation methodfollowing standard coacervation methods disclosed in U.S. Pat. No.4,010,242 to Iler et al., except solid cores were added in thecoacervation mixture. Specifically, 66.36 g of the above cores made fromExample 1 were added into 1900 g of 2 nm sol (4.84% SiO₂, 127.6 g SiO₂)in a beaker, and were sonicated for 10 to 15 minutes to make sure thecores broke apart into single particles (checked by microscope andCoulter). The mixtures of the cores and the sol solution were pouredinto a big container, followed by addition of 3617 g of water and 70 gof urea. The mixture was stirred until urea was dissolved. 92.4 g of 70%nitric acid was poured into the mixture under rapid stirring. After 30seconds, 122.7 g of formaldehyde were poured into the mixture. Themixture was kept under rapid stirring for 30 seconds, and then wasallowed to sit still overnight. The particles grew from 1.9 μm solidcores to 3.4 μm raw particles. A second population of fine particles in1.1 to 1.3 μm size was also formed in the mixture. The supernatant wasremoved, and the particles were reslurried in water. The smallerparticles were removed from the coated raw particles by eithercentrifugation several times or water elutriation fractionation. Thecoated raw particles were heated at 600° C. for 10 hours to burn off theurea/formaldehyde polymer, and sintered at 1000° C. for 2 to 3 hours forstrengthening. The surface of the sintered particles was thenrehydroxylated by diluted hydrofluoric acid method described in J.Kohler and J. J. Kirkland, J. Chromatograr., 385 (1987) 125-150. Afterliquid elutriation fractionation to eliminate aggregated particles andfine particles, the particles demonstrated an average particle size of2.68 gm±6% (one sigma) as measured by Coulter Counter (see FIG. 4). Thenitrogen surface area of these particles was 136 m²/g and average poresize of 126 Å as measured by the Tristar instrument (Micromeritics,Norcross, Ga.). Based on the diameter of the final particles (2.7 μm),it was calculated that the thickness of the porous shell coating on thesolid cores was 0.5 μm. Scanning electron microscopy of these particlesis shown in FIG. 2.

Example 4 Preparation of Superficially Porous Particles (II)

2.0 μm superficially porous silica particles with 1.0 μm solid cores and0.5 μm thickness shell were prepared from the cores in Example 2 usingthe procedure in example 3. The particles were sintered at 1040° C. for6 hours. The nitrogen surface area of the particles was 120 m²/g, porevolume was 0.512 cm³/g, and average pore size was 140 Å as measured bythe Tristar instrument (Micromeritics, Norcross, Ga.).

Example 5 Preparation of Superficially Porous Particles (III)

Superficially porous silica particles were also prepared by gradualaddition of urea and formaldehyde solution into the cores to graduallygrow the shell to the desired thickness. 474 g of water, 58 g ofethanol, 46 g of 2 nm sol (5.7% SiO2) and 5 g of surface modified coresin Example 1 were mixed as solution A, and sonicated for 20 minutes.Solution B comprised 289 g of water, 100 g of 2 nm sol, 8.4 g of ureaand 12.6 g of formaldehyde solution mixed together until the ureadissolved. Solution A was set up with a polyethylene stir blade mixingat 200 rpm. 17.5 g of 70% nitric acid was added to solution A. SolutionB was then gradually pumped into solution A with continuous stirringover ˜40 minutes. After a total of 70 minutes from the beginning ofsolution B addition, the stir blade was removed and the particles wereallowed to settle overnight. The particles grew to size in 3.3-3.6 μmwith second population of fine particles in ˜1.0 μm size. Thesupernatant was removed, and the particles were processed as in Example3.

Example 6 Preparation of Superficially Porous Particles (IV)

2.7 μm superficially porous particles were prepared using 8 nm sol(4.64% SiO2) according to Example 3. The final particle surface area was130 m2/g, pore volume was 0.40 cm3/g, and pore size was 120 Å.

Example 7 Preparation of a Separation Device Using the SuperficiallyPorous Particles

A separation device was prepared and analysed using the superficiallyporous particles. Specifically, 2.7 μm superficially porous particles asprepared in Example 3 were bonded withn-octadecyldimethyl(dimethylamino)silane (Gelest, catalog #SIO6617.0)and endcapped with (n,n-dimethylamino)dimethylsilane (Gelest, catalog#SID3546.6) using standard bonding and endcapping procedures. A sampleof the bonded and endcapped particles was loaded into a 4.6×50 mm columnusing the slurry packing method described in J. J. Kirkland and J. J.DeStefano, J. Chromatogr. A, 1126 (2006) 50-57. The final column wastested with a model 1200 HPLC system (Agilent Technologies) using 60%acetonitrile/40% water as the mobile phase at 24° C. At a flow rate of 2ml/min, this column demonstrated 12,000 theoretical plates usingnaphthalene as the solute, representing a column performance with areduced plate height of 1.5.

The performance of the column of superficially porous particles wascompared with those of totally porous silica particles in 1.8 μm and 3.5μm diameters (both were Zorbax Eclipse Plus C18 from AgilentTechnologies). All the columns were in 4.6×50 mm format. FIGS. 5 and 6show van Deemter plots of for the columns. The data show that theinventive superficially porous particles exhibit plates superior to the3.5 μm totally porous particles, and similar to 1.8 μm totally porousparticles, while maintaining a much lower back pressure than that of the1.8 μm totally porous particles.

1. A method for making superficially porous particles, comprisingattaching an organic surface modifier to a solid metal oxide coreparticle to provide a surface modified solid metal oxide core particle;forming a coating on the surface modified solid metal oxide coreparticle, wherein the coating comprises a continuous polymeric phasebonded to the organic surface modifier and a particulate phase dispersedwithin the continuous polymeric phase; and removing the continuouspolymeric phase from the coating to provide a superficially porousparticle.
 2. The method of claim 1, wherein the organic surface modifieris bonded to the solid metal oxide core particle.
 3. The method of claim2, and wherein the organic surface modifier comprises an organosilaneresidue.
 4. The method of claim 2, wherein the solid metal oxide coreparticle comprises silica, and the organic surface modifier comprises anorganosilane covalently bonded to the surface of the solid metal oxidecore particle.
 5. The method of claim 2, wherein the organic surfacemodifier comprises a ureido residue.
 6. The method of claim 2, whereinthe organic surface modifier comprises an oligo- orpoly(urea-formaldehyde).
 7. The method of claim 1, wherein the solidmetal oxide core particle comprises one or more of silica, alumina,titania, zirconia, ferric oxide, antimony oxide, zinc oxide, or tinoxide.
 8. The method of claim 1, wherein the organic surface modifiercomprises an oligo- or poly(urea-formaldehyde).
 9. The method of claim1, wherein the organic surface modifier is physisorbed to the solidmetal oxide core particle.
 10. The method of claim 1, wherein the solidmetal oxide core particle comprises one or more surface hydroxyl groups,and wherein attaching an organic surface modifier to the solid metaloxide core particle comprises reacting the one or more surface hydroxylgroups with one or more organic residues.
 11. The method of claim 1,wherein forming the coating on the surface modified solid metal oxidecore particle comprises contacting the organic surface modifier with oneor more polymerizable residues.
 12. The method of claim 11, wherein theone or more polymerizable residues comprise urea, formaldehyde,melamine, or a mixture thereof.
 13. The method of claim 1, whereinforming the coating on the surface modified solid metal oxide coreparticle comprises contacting the organic surface modifier with acomposition comprising one or more polymerizable residues and one ormore nano-sized metal oxide particles.
 14. A plurality of superficiallyporous particles; wherein at least one of the superficially porousparticles is aggregated with a smaller totally porous particle.
 15. Theparticles of claim 14, wherein the superficially porous particlescomprise substantially solid cores having: a) a size ranging from about20% to about 99% of the size of the total particle size; b)substantially porous outer shells having ordered pores with a medianpore size ranges from about 15 to about 1000 Å with a pore sizedistribution (one standard deviation) of no more than 50% of the medianpore size. c) wherein the particles have a specific surface area of fromabout 5 to about 1000 m²/g; and d) wherein the particles have a mediansize range from about 0.5 μm to about 100 μm with a particle sizedistribution (one standard deviation) of no more than 15% of the medianparticle size;
 16. The particles of claim 14, wherein the superficiallyporous particles have a diameter from about 0.5 μm to about 10 μm. 17.The particles of claim 14, wherein the superficially porous particlescomprise one or more of silica, alumina, titania, zirconia, ferricoxide, antimony oxide, zinc oxide, or tin oxide.
 18. A separation devicehaving a stationary phase comprising a plurality of superficially porousparticles; wherein at least one of the superficially porous particles isaggregated with a smaller totally porous particle.
 19. The separationdevice of claim 18, wherein the superficially porous particles comprisesubstantially solid cores having a) a size ranging from about 20% toabout 99% of the size of the total particle size; b) substantiallyporous outer shells having ordered pores with a median pore size rangesfrom about 15 to about 1000 Å with a pore size distribution (onestandard deviation) of no more than 50% of the median pore size. c)wherein the particles have a specific surface area of from about 5 toabout 1000 m²/g; and d) wherein the particles have a median size rangefrom about 0.5 μm to about 100 μm with a particle size distribution (onestandard deviation) of no more than 15% of the median particle size; 20.The separation device of claim 18, wherein the superficially porousparticles comprise one or more of silica, alumina, titania, zirconia,ferric oxide, antimony oxide, zinc oxide, or tin oxide.